Chicago, IL - Childhood cancer survivors are at increased risk of developing premature cardiovascular disease and hence need to be closely monitored after their treatment and followed appropriately as they age, concludes the largest and longest study of this population [1].

The findings, from the Childhood Cancer Survivor Study, are scheduled to be presented June 3, 2008 at the American Society of Clinical Oncology (ASCO) 2008 Annual Meeting and were unveiled last week during a preview presscast organized by the society.

The study followed 14 358 survivors of various childhood cancers and compared them with 3899 siblings. The diagnoses included childhood leukemia, central nervous system tumors, Hodgkin's and non-Hodgkin's lymphomas, renal tumors, neuroblastomas, soft-tissue sarcomas, and bone cancers. The average age of study participants at diagnosis was 7.8 years, and the mean age at follow-up was 27.5 years, so the mean follow-up period was nearly 20 years.

Cardiovascular monitoring of childhood cancer survivors should begin early and should be life-long.

The risk for cardiovascular disease was significantly greater in survivors than in siblings. The risk for atherosclerosis was 10 times greater, for congestive heart failure 5.7 times greater, for MI 4.9 times greater, for pericardial disease 6.3 times greater, and for valvular disease 4.8 times greater.

"This study shows that childhood cancer survivors in their 20s are developing the kinds of heart disease we typically see in older adults," commented lead investigator Dr Daniel Mulrooney (University of Minnesota, Minneapolis). The risk for cardiovascular disease increased with time, and some of these problems appear quite late, he continued.

"Cardiovascular monitoring of childhood cancer survivors should begin early and should be lifelong," Mulrooney stated. He estimated that there are currently 270 000 childhood cancer survivors in the US.

Studies of childhood cancer survivors have identified long-term problems that can unfold as children grow into adulthood. In addition to cardiovascular problems, these include an increased risk for secondary cancers, infertility, lung scarring, thyroid problems, and psychological problems such as depression and anxiety, commented Dr Julie Gralow (University of Washington, Seattle), who moderated the presscast.

Being a cancer survivor is a very special diagnosis in many ways.

"Being a cancer survivor is a very special diagnosis in many ways," Gralow commented, "and brings with it a responsibility to understand the long-term consequences of cancer treatment and to monitor these patients appropriately for any problems they may develop.

"Many patients, as they continue with their lives, tend to transfer their medical care to primary-care physicians and to discontinue relationships with their oncologists or maintain them very infrequently, as would be appropriate for someone who is . . . cured of their cancer," she continued. "But it then becomes incumbent on patients and their primary-care physicians to be aware of their cancer history and their cancer treatment and the potential consequences of that treatment.

"ASCO is working very hard to develop a template for a cancer-survivor care plan," Gralow noted. It will contain details of the cancer that the patient had, the treatment received, and the potential consequences. The patient will have this document and will be able to present it to any doctor who becomes involved in his or her care.

The highest risk for cardiovascular disease was seen in survivors who had undergone treatment with either anthracyclines (doses above 250 mg/m²) or radiation to the heart area (doses above 3500 Gy). These individuals had a two- to fivefold increased risk for cardiovascular disease, compared with survivors who underwent other types of treatment.

Anthracyclines are already known for their cardiotoxic effects, Mulrooney commented; previous studies have shown a risk for dilated myopathy and congestive heart failure, and this seems to be progressive over time. The mechanism is thought to involve iron deposited in the heart, but more work needs to be done on this, he said. The damage from radiation seems to be inflicted on the pericardium and the epithelial lining of blood vessels, and the vessel disease seen in these young adult cancer survivors is different from what would be seen in an older population with cardiovascular disease, he commented.

"Typically, in these older patients, on a coronary angiogram, you would see diffuse disease and lipid deposits that have occurred over time; in cancer survivors who have received chest radiation, you typically see injury to the coronary artery and deposits that are very proximal to the heart. Why this is the case is not clear at the current time," he said.

Children in this study were treated between 1970 and 1986, and therapy has changed since then, Mulrooney commented. "We now have more targeted therapies and new . . . ways to give radiation therapy that give off less scatter, hopefully less scatter to the heart itself. And we have different ways of administering drugs—for example, continuous infusions instead of bolus doses," he commented. "We don't know yet what the long-term results will be with these new modalities. But hopefully they will maintain the efficacy that we have seen while reducing the long-term adverse effects."

Mulrooney emphasized that although the risk for heart disease is significantly increased in survivors, the overall risk of developing cardiovascular problems is low. Thirty years after a diagnosis of childhood cancer, 2% of survivors had atherosclerosis, 4% had congestive heart failure, 1% had an MI, 3% developed pericardial disease, and 4% had valvular heart disease.